Related Experiment Video
Updated: Dec 2, 2025
08:54
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells
Published on: July 20, 2014
14.3K
GDF6-CD99 Signaling Regulates Src and Ewing Sarcoma Growth.
Fuchun Zhou1, David J Elzi2, Panneerselvam Jayabal1
1Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Cell Reports
|November 4, 2020
Summary
Growth differentiation factor 6 (GDF6) prodomain binds CD99 to inhibit Src activity, maintaining Ewing sarcoma growth. This discovery reveals a new therapeutic target for Ewing sarcoma by modulating the CD99-Src signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Ewing sarcoma is a pediatric bone cancer.
- Growth differentiation factor 6 (GDF6) is a cytokine in the bone morphogenetic protein (BMP) family.
- CD99 is a cell surface marker for Ewing sarcoma.
Purpose of the Study:
- To investigate the role of GDF6 in Ewing sarcoma growth.
- To identify the specific domain of GDF6 involved in Ewing sarcoma.
- To elucidate the mechanism by which GDF6 regulates Ewing sarcoma proliferation.
Main Methods:
- Western blotting to assess protein levels and phosphorylation.
- Immunoprecipitation to study protein-protein interactions.
- Cell viability assays to measure proliferation.
Main Results:
- Ewing sarcoma growth depends on the GDF6 prodomain, not the BMP domain.
- The GDF6 prodomain directly binds to CD99 on Ewing sarcoma cells.
- GDF6 prodomain binding to CD99 recruits C-terminal Src kinase (CSK), inhibiting Src activity and preventing p21-dependent growth arrest.
- GDF6 silencing leads to Src hyperactivation and growth arrest.
- Klippel-Feil syndrome-associated GDF6 mutants show enhanced CD99-Src signaling.
Conclusions:
- The GDF6 prodomain-CD99 interaction is crucial for maintaining Ewing sarcoma growth by regulating the CSK-Src axis.
- This pathway represents a potential therapeutic target for Ewing sarcoma.
- Gain-of-function mutations in GDF6 prodomain can drive disease pathogenesis.
Related Concept Videos
02:38Mitogens and the Cell Cycle
7.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.5K
01:16TGF - β Signaling Pathway
9.7K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
9.7K
03:03mTOR Signaling and Cancer Progression
4.3K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.3K
02:54Canonical Wnt Signaling Pathway
9.9K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.9K
01:24Regulation of Angiogenesis and Blood Supply
3.1K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.1K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.5K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.5K